"Langerhans cells (LC) are members of the dendritic cell (DC) family and function as the major antigen presenting cells of epidermis and genital mucosal surfaces. It is generally believed that LC are the initial target cells for HIV following mucosal exposure to virus. My lab is focused on studying how HIV interacts with LC and other DC, with the hope that this work will add insight into the early events involved in HIV primary infection. In the past year, we have published three papers on this topic and have one paper in press. Using LC-like DC (propagated from normal blood DC precursors), we have shown that productive infection by HIV and their ability to capture virus are mediated through separate processes. The in vivo relevance of each particular pathway is currently being investigated. We have also studied HIV co-receptor surface expression and function in detail on LC and DC. Interestingly, freshly isolated epidermal LC (which resemble LC located in mucosa) express cell surface CCR5, the major HIV co-receptor for macrophage-tropic strains of HIV, but do not express cell surface CXCR4, the major HIV co-receptor for T cell-tropic strains of HIV. This finding may help to explain why macrophage-tropic strains of HIV are preferentially transmitted during sexual transmission of HIV. Using LC derived from skin, we have also shown that HIV co-receptor expression and function can be differentially modulated by type 1 and type 2 cytokines, a finding which may have relevance for the development of AIDS in HIV-infected individuals. Recently, we have examined the effects of HIV and human herpesvirus 6 (a possible co-factor in the pathogenesis of AIDS) on DC viability and function in co-infection studies. Current studies are centered on the development of more physiologic models of primary HIV infection. To this end, we are using primary isolate strains of HIV to infect immature LC within epithelial sheets and have used this model to test potential topical microbicides designed to prevent sexual transmission of HIV. As well, we have begun in vitro infections of vaginal and cervical mucosal tissue (obtained from healthy human volunteers and surgical specimens). In summary, we have used epidermal LC, mucosal LC, and blood-derived LC-like DC to model early biologic events that may be occurring during primary HIV infection. This work may ultimately lead to the design and development of specific strategies aimed at blocking this process. ""HIV/AIDS"""